Non-alcoholic fatty liver disease (
NAFLD) is a prevalent chronic liver condition that can have multiple underlying causes. There are no satisfactory chemical or biological drugs for the treatment of
NAFLD. Longyasongmu, the bark and root of Aralia elata (Miq.) Seem, is used extensively in
traditional Chinese medicine (TCM) and has been used in treating diverse
liver diseases including
NAFLD. Based on Aralia elata (Miq.) Seem as the main ingredient, Longya Gantai Capsules have been approved for use in China for the treatment of acute
hepatitis and
chronic hepatitis.
Calenduloside E (CE), a natural pentacyclic
triterpenoid saponin, is a significant component of
saponin isolated from the bark and root of Aralia elata (Miq.) Seem. However, the role and mechanism of anti-
NAFLD effects of CE is still unclear.
AIM OF THE STUDY: In this study, an
NAFLD model was established by Western diet in
apoE-/- mice, followed by treatment with various doses of CE (5 mg/kg, 10 mg/kg). The anti-
NAFLD effect of CE was assessed by the liver injury,
lipid accumulation,
inflammation, and pro-fibrotic phenotype. The mechanism of CE in ameliorating
NAFLD was studied through transcriptome sequencing (
RNA-seq). In vitro, the mouse hepatocytes (AML-12) were stimulated in
lipid mixtures with CE and performed the exploration and validation of the relevant pathways using Western blot, immunofluorescence, etc. RESULTS: The findings revealed a significant improvement in liver injury,
lipid accumulation,
inflammation, and pro-fibrotic phenotype upon CE administration. Furthermore, RNAseq analysis indicated that the primary pathway through which CE alleviates
NAFLD involves pyroptosis-related inflammatory cascade pathways. Furthermore, it was observed that CE effectively suppressed
inflammasome-mediated pyroptosis both in vivo and in vitro. Remarkably, the functional enrichment analysis of
RNA-seq data revealed that the PI3K-Akt signaling pathway is the primarily Signaling transduction pathway modulated by CE treatment. Subsequent experimental outcomes provided further validation of CE's ability to hinder
inflammasome-mediated pyroptosis through the inhibition of PI3K/AKT/NF-κB signaling pathway.
CONCLUSIONS: